Breakthrough in cancer treatment prolongs the life of terminally ill dogs

Canine cancer is the leading cause of death in dogs, as well as when they are diagnosed with an advanced stage or incurable disease. (CREDIT: Shutterstock)

Dogs are people’s best friends, and dog owners are always saddened when their beloved pets fall ill with an incurable disease. Canine cancer is the leading cause of death in dogs, and when they are diagnosed with an advanced stage or incurable disease, there are often no treatment options available. However, in a recent study, a new form of chemoimmunotherapy has shown promise for changing the course of a dog’s life.

Scientists at the NUS Center for Cancer Research (N2CR) under the Translational Research Program (TRP) of the Yong Lu Lin School of Medicine at the National University of Singapore (NUS Medicine) have used precision-engineered stem cell technology to treat cancer patients in dogs.

In a study led by Associate Professor Tu Heng-Fong of N2CR TRP and NUS Medicine’s Department of Biochemistry, the team modified mesenchymal stem cells (MSCs) that are capable of detecting cancerous tumors. These modified cells carry a powerful “switch” (cytosine deaminase) that produces a high localized concentration of the cancer-killing drug (5-fluorouracil) in the tumor environment and subsequently induces anti-cancer immunity.

The development of this therapy for canine patients is leading the team to a better understanding of cancer treatments as well as its use in human patients, as helping dogs with natural cancers provides valuable information about human cancer.

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Associate Professor Tu said: “To repurpose stem cells for cancer treatment, viruses are commonly used to inject therapeutic genes into the cells. However, we have developed a non-viral gene delivery platform that injects large numbers of therapeutic genes into stem cells to effectively kill out-of-control cancer cells. With this therapy, which has been proven to be safe and has shown promising clinical benefits in animal patients, we hope to develop effective treatment options that also benefit cancer patients that can improve their health without compromising their quality of life.”

Application of the technology to dogs with cancer

The technology developed by the NUS Medicine team was first applied to dogs in Singapore in 2018 in collaboration with Dr. Jean Paul Lee, CEO and founder of Animal Wellness.

Since then, the research team has collaborated with other veterinary partners and institutions treating a total of 65 dogs as well as two cats with conditions such as perianal adenoma, lung metastases and sarcoma.

Initially, patients received precisely engineered MSCs by direct injection into the tumor or through the bloodstream, followed by several days of oral tablets containing a drug commonly used to treat fungal infections (5-flucytosine). A week later, the cycle was repeated for another two weeks before the first course of treatment was completed. The team then monitored the condition of the patients and repeated the course if necessary.

Among animal patients treated for a period of three to eight weeks, 56 showed signs of a positive response, including 14 who recovered completely after treatment. Two animal patients were cancer-free at least 30 months after treatment, while 46 patients showed a good quality of life for two to 32 months after treatment. No significant side effects were observed during the treatment of all animal patients in the study, possibly due to the localized presence of therapeutic cells that remain in the tumor environment.

Despite significant advances in the treatment of cancer in humans, there is a significant backlog in the development of oncological treatments in animals. Up until 2009, all animals were treated with off-label generic human chemotherapy drugs because there were no animal-specific anti-cancer drugs approved by the US Food and Drug Administration (FDA).

Dr Li Yi Ling, founder and chief executive officer of the Gentle Oak Veterinary Clinic in Singapore, with whom the research team collaborated and who is one of the authors of the study, said: “Therapies and advances in allopathic medicine are usually developed for humans first, before they apply to animals. However, in the trials for this study, dogs with cancer who have no other available treatment options are the main recipients of the therapy, and many of them have shown promising results with improved quality of life. We hope that in the near future this therapy will become one of the standard options available for dogs and it will benefit more patients.”

One of the team’s partners, Associate Professor Antonio Giuliano from the Department of Veterinary Clinical Sciences, City University of Hong Kong, will also be applying the therapy in animal clinical trials in 2023.

Providing Therapy as an Accessible and Accessible Option for Human Patients

Stem cell modification therapy is different from other cell and gene therapies that use viruses to introduce genes into cells. Instead of using a virus, the modification involves the use of a chemical carrier that is safer and faces fewer regulatory restrictions when developing a treatment. Compared to other cell and gene therapies, the therapy regimen has a significantly shorter cycle time and much lower production costs, paving the way for a more affordable and affordable option for cancer patients in the future.

Dr. Ho Yun Khei, Senior Research Fellow at N2CR TRP and NUS Medicine’s Division of Biochemistry, as well as the study’s first author and lead researcher, said: “Currently, we can develop this therapy for 18 patients each week. In addition to the results that have shown benefit to our companion animals, we hope to expand the therapy to human patients in the future and improve treatment outcomes for those with cancer, especially when they have no treatment options left.”

The research team is working with local and global health agencies to analyze the safety and efficacy of veterinary therapies and discuss plans for human clinical trials in Singapore and the Asia-Pacific region. They are expected to start in 2024.

Professor Chong Yap Seng, Lien Ying Chow Professor of Medicine, Dean of the NUS School of Medicine, added: “Our research work at NUS Medicine is focused on creating real, meaningful health benefits for the population we serve and ultimately improving health outcomes for all. We believe that this therapy, developed by N2CR, will have a major impact on the health and well-being of patients with advanced tumors and advanced cancers.”

N2CR is one of 10 Translational Research Programs (TRPs) at NUS Medicine aimed at building a solid and consistent scientific base for effective and meaningful research outcomes for Singapore’s school and healthcare system. Other than cancer, other areas are cardiovascular disease, digital medicine, healthy aging, human potential, immunology, infectious disease, precision medicine, synthetic biology, and nanomedicine.

These 10 key priority areas, which are interdisciplinary and based on health and disease, will create greater synergy and collaboration between basic scientists and clinical scientists, strengthen programmatic research, and provide research results to address clinically relevant issues and applications that are aligned with national priorities. .

For more science and technology news, visit our New Innovations section at The bright side of the news.

Note: Materials provided above by the National University of Singapore. Content can be edited for style and length.

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